Fighting Two Addictions with One Pill?

Since its approval by the FDA in 2006, varenicline has become a valuable aide for people trying to get over the hump of quitting smoking. Marketed as Chantix, the drug has joined buproprion and nicotine replacement therapy as popular options for helping smokers fight cravings and withdrawal as they try to kick the habit. But like any drug, varenicline has its side effects: most commonly nausea, with some rare occurrences of things like constipation, abdominal pain, and depression. But one unexpected side effect of varenicline upon a complete different vice may in fact turn out to be a secondary use for the drug.

In addition to helping them avoid nicotine, patients taking Chantix sometimes report that the drug cuts down on their drinking, taking some of the joy out of cocktail hour. Some researchers have chased this lead down in animal and human research, finding that rats will consume less alcohol after treatment with varenicline and that heavy-drinking smokers on the medication report reduced craving for alcohol. But nobody had yet looked at exactly why varenicline puts people off of booze, or what a single dose of the drug could do compared to the prolonged exposure a smoker experiences during a Chantix prescription.

To answer these questions, a team led by Emma Childs, research associate (assistant professor) in the Department of Psychiatry at the University of Chicago Medicine, recruited 15 moderate-to-heavy social drinkers for a controlled laboratory experiment. Each subject spent six afternoons in the lab, receiving a dose of varenicline or placebo in each session, and then three hours later drinking either a non-alcoholic beverage or a drink containing one of two different concentrations of alcohol. Researchers monitored the subjects’ blood pressure, heart rate, and eye movements for an objective take on how the alcohol affected their system, and also asked questions about their enjoyment of the drink and its effects.

The results, published this week in the journal Alcoholism: Clinical and Experiment Research, determined that varenicline keeps people off the bottle by bringing out the worst effects of alcohol. Compared to placebo, varenicline increased feelings of nausea in the subjects even before receiving an alcoholic drink — a known side effect of the drug. But even when researchers controlled for the effects of this nausea, the subjects reported increase dysphoria (the opposite of euphoria) after drinking an alcoholic drink, and reported enjoying the drink less than on the afternoons where they were pre-treated with placebo. Eye movements associated with alcohol were also lessened by varenicline, implying that the drug interferes with objective effects of the substance as well as self-reported effects.

By reducing the allure of alcohol, varenicline might help people prone to binge drinking say no to subsequent drinks by ruining the good vibes of the night’s first cocktail.

“Our findings shed light on the mechanism underlying why people consume less alcohol when they have taken varenicline,” said Childs. “The pleasurable effects of alcohol, for example feeling ‘buzzed’ and talkative, are associated with greater consumption and binge drinking. Some people lose control of their alcohol consumption during a drinking episode, for example they may aim to only have one or two drinks but end up drinking say four or five. If varenicline counteracts these positive effects by producing unpleasant effects, then as a result people may consume less alcohol during a drinking episode.”

The overlapping effects of varenicline upon smoking and drinking also shed light on an interesting neurobiological phenomenon: how these two addictions dovetail in the brain. Previous research by one of the study’s co-authors, Andrea King, explored the social link between drinking and smoking, finding that drinking alcohol does increase the urge to smoke in casual, social smokers. Varenicline curbs cigarette craving by partially activating the receptor for nicotine in the brain, and the drug’s influence upon the effects of alcohol and craving for a drink suggest that this nicotinic receptor also plays a somewhat unexpected role in how alcohol affects the brain. This neurobiological clue could point the way to even more effective therapies to help alcoholics quit drinking.

As for expanding the use of varenicline into this new patient population, the authors cautioned that their study only examined the acute effect of a single dose of varenicline, rather than the sustained exposure experienced with regular use of the drug. But because the effectiveness of varenicline has already been proven as a smoking cessation drug, the unanticipated effects on drinking may make people struggling with both behaviors a logical first target.

“Varenicline may find a nice niche in those individuals who are both nicotine and alcohol dependent, who we know represent a large portion of alcohol-dependent individuals,” commented Hugh Myrick, associate professor of psychiatry at the Medical University of South Carolina, who was not involved in the study. “Since there is a high comorbidity between nicotine and alcohol dependence, a single medication that could decrease the use of both substances would be ideal.”